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Association of reduced maternal sHLA-G5 isoform levels and elevated TNF-α/IL-4 cytokine ratio with Recurrent Pregnancy Loss: A study on South Indian women
Scandinavian Journal of Immunology ( IF 3.7 ) Pub Date : 2021-08-09 , DOI: 10.1111/sji.13095
Dhatri Madduru 1 , Kethora Dirsipam 2 , Mahalakshmi Goli 3 , Venkata Ramana Devi 1 , Parveen Jahan 4
Affiliation  

Inflammation is of critical importance in successful implantation during pregnancy. However, the establishment of maternal immune tolerance towards semi-allograft foetus is more exigent and is achieved predominantly by human leukocyte antigen-G (HLA-G) isoforms with a special emphasis on soluble HLA-G5 (sHLA-G5). Constant inflammation and lack of resolution by anti-inflammatory milieu, due to aberrant expression of critical immunoregulatory molecules such as sHLA-G5 and dysfunctional T helper cells 1 and 2 (Th1-Th2) cytokine shift, can lead to adverse pregnancy outcomes including recurrent pregnancy loss (RPL). Serum samples of 270 pregnant women (135 healthy parous and 135 with a history of RPL) were evaluated for the concentrations of sHLA-G5, interleukin-4 (IL-4) and tumour necrosis factor-alpha (TNF-α) using sandwich enzyme-linked immunosorbent assay (ELISA) and found elevated levels of sHLA-G5 and IL-4 in controls and higher TNF-α levels and TNF-α:IL-4 ratio in patients (P < .05). Stratified data analysis based on the time of sample collection, that is the first and second trimesters exhibited higher sHLA-G5 and IL-4 in both first and second trimesters in controls than patients, while they displayed lower levels concerning TNF-α and TNF-α:IL-4 ratio (P < .05). However, within patients and controls in the first or second trimesters, there was a significant variation concerning sHLA-G5 alone. Further, the outcome of pregnancies studied in the present investigation revealed a significant elevation in sHLA-G5 levels among women with successful pregnancies compared with women who experienced pregnancy loss, therefore, concluding the potential application of sHLA-G5 isoform as a marker in assisting improved pregnancy outcomes.

中文翻译:

母体 sHLA-G5 亚型水平降低和 TNF-α/IL-4 细胞因子比率升高与复发性妊娠丢失的关联:一项针对南印度妇女的研究

炎症对于怀孕期间的成功植入至关重要。然而,对半同种异体移植胎儿的母体免疫耐受的建立更为迫切,主要通过人类白细胞抗原-G (HLA-G) 同种型实现,特别强调可溶性 HLA-G5 (sHLA-G5)。由于 sHLA-G5 等关键免疫调节分子的异常表达和功能失调的 T 辅助细胞 1 和 2 (Th1-Th2) 细胞因子转变,持续炎症和抗炎环境无法解决,可导致不良妊娠结局,包括反复妊娠损失(RPL)。评估了 270 名孕妇(135 名健康经产者和 135 名有 RPL 病史)的血清样本的 sHLA-G5 浓度,P  < .05)。基于样本采集时间的分层数据分析,即在妊娠早期和中期,对照组在早期和中期的 sHLA-G5 和 IL-4 均高于患者,而他们在 TNF-α 和 TNF-α 方面的水平较低α:IL-4 比率 ( P  < .05)。然而,在妊娠早期或中期的患者和对照组中,单独使用 sHLA-G5 存在显着差异。此外,本调查中研究的妊娠结果显示,与经历流产的女性相比,成功妊娠的女性的 sHLA-G5 水平显着升高,因此,得出结论认为 sHLA-G5 同种型作为标记物有助于改善妊娠的潜在应用怀孕结果。
更新日期:2021-09-15
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